Our overall aim is to understand the molecular events that underlie[unreadable] glutamate receptor mediated signal transduction in the brain. In[unreadable] particular, we have studied the effect of glutamate receptor activation[unreadable] on the concentration of neuronal Ca, (Ca)i, and resulting effects on the[unreadable] state of neuronal mitochondria and the production of superoxide and[unreadable] other reactive oxygen species (ROS).[unreadable] [unreadable] In the present proposal we shall be interested in understanding how[unreadable] these events may be involved in glutamate receptor mediated excitotoxic[unreadable] neuronal degeneration, a process that is believed to be extremely[unreadable] important in many types of neurodegenerative diseases including stroke[unreadable] and epilepsy.[unreadable] We shall use imaging procedures to examine how the activation of[unreadable] glutamate receptors in the brain can regulate the state of mitochondria[unreadable] and the production of ROS and how these processes are regulated. We[unreadable] shall also be interested in how these processes can be altered by[unreadable] activation of the metabotropic glutamate receptors that are also[unreadable] stimulated by synaptically released glutamate.[unreadable] [unreadable] We shall further investigate the importance of Ca and ROS by[unreadable] manipulating the concentrations of key neuronal proteins such as[unreadable] superoxide dismutase and nitric oxide synthase using an adenovirus[unreadable] expression system.[unreadable] Overall we hope that these studies will increase our understanding of[unreadable] glutamate mediated signal transduction in the brain and its role in[unreadable] neurodegenerative disease.